New Insights into Xantphos/Pd-Catalyzed C−N Bond Forming Reactions: A Structural and Kinetic Study

Both (Xantphos)Pd(dba) and Pd(Xantphos)2 were identified in mixtures of Pd2(dba)3 and Xantphos by
use of 31P NMR and independent syntheses. At high ligand concentrations, Pd(Xantphos)2 was found to
be the predominant species. Reaction calorimetry was employed to determine whether the formation of
Pd(Xantphos)2 affects the rate at which the Pd-catalyzed C−N bond formation occurs between 4-tert-butylbromobenzene and morpholine. Indeed, the concentration of Xantphos dramatically influences the
activity of the catalyst, with high concentrations of Xantphos inhibiting the reaction rate due to the
formation of Pd(Xantphos)2. Two plausible hypotheses for the low activity of Pd(Xantphos)2 as a precatalyst
are (1) a slow rate of Xantphos dissociation from Pd(Xantphos)2 inhibits the formation of an active
(Xantphos)Pd0 species and (2) the high degree of insolubility of Pd(Xantphos)2 results in the precipitation
of a significant fraction of the precatalyst from the reaction mixture. Although the equilibrium constant
for ligand dissociation could not be determined by either magnetization transfer or variable-temperature
experiments due to its slow rate, the more soluble Pd(4,7-di-tert-butylXantphos)2 complex demonstrated
different activity relative to Pd(Xantphos)2. A comprehensive study of these two complexes indicates
that the lower activity of the bis-ligated Pd species is a result of a combination of aforementioned processes,
i.e., the slow rate of ligand dissociation and the insolubility of Pd(Xantphos)2, with the rate of ligand
dissociation serving as the primary turnover-limiting factor.